Abstract
The rise of optogenetics provides unique opportunities to advance materials and biomedical engineering, as well as fundamental understanding in neuroscience. This protocol describes the fabrication of optoelectronic devices for studying intact neural systems. Unlike optogenetic approaches that rely on rigid fiber optics tethered to external light sources, these novel devices carry wirelessly powered microscale, inorganic light-emitting diodes (μ-ILEDs) and multimodal sensors inside the brain. We describe the technical procedures for construction of these devices, their corresponding radiofrequency power scavengers and their implementation in vivo for experimental application. In total, the timeline of the procedure, including device fabrication, implantation and preparation to begin in vivo experimentation, can be completed in ∼3–8 weeks. Implementation of these devices allows for chronic (tested for up to 6 months) wireless optogenetic manipulation of neural circuitry in animals navigating complex natural or home-cage environments, interacting socially, and experiencing other freely moving behaviors.
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Acknowledgements
This work is supported by the US National Institutes of Health Common Fund; the National Institute on Drug Abuse (NIDA) grant no. R01DA037152 (M.R.B.); NIDA grant no. R00DA025182 (M.R.B.); National Institute of Neurological Disorders and Stroke (NINDS) grant no. R01NS081707 (M.R.B., J.A.R.); National Institute of Mental Health (NIMH) grant no. F31MH101956 (J.G.M.); the McDonnell Center for Systems Neuroscience (M.R.B.); a National Security Science and Engineering Faculty Fellowship of Energy (J.A.R.); the US Department of Energy, Division of Materials Sciences under award no. DE-FG02-07ER46471 (J.A.R.); the Materials Research Laboratory and Center for Microanalysis of Materials (DE-FG02-07ER46453) (J.A.R.) and the Washington University in St. Louis Division of Biological and Biomedical Sciences (J.G.M.); and the Institute for Basic Science (IBS) (T-i.K.) and National Research foundation of Korea Grant funded by the Ministry of Science, ICT and Future Planning (2009-0083540) in Korea (T-i.K.). We thank H. Tao (Tufts University) and S. Hwang (University of Illinois at Urbana-Champaign) for their help in the preparation of silk solution and for valuable discussions. We thank A.M. Foshage, E.R. Siuda and other members of the Bruchas laboratory, the laboratory of R.W. Gereau, IV (Washington University in St. Louis) and the laboratory of G.D. Stuber (University of North Carolina) for helpful discussion and technical advice. We also thank K. Deisseroth (Stanford University) for the channelrhodopsin-2 (H134) constructs, the Stuber laboratory for the TH-IRES-Cre mice, the Washington University in St. Louis Bakewell Neuroimaging Laboratory Core, the Washington University in St. Louis Machine Shop and the Washington University in St. Louis` Hope Center Viral Vector Core.
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J.G.M., T-i.K., G.S., X.H., Y.H.J. and R.A.-H. performed the experiments. J.G.M., T-i.K., G.S., X.H., R.A.-H., F.G.O., M.R.B. and J.A.R. developed the protocol. J.G.M., T-i.K., G.S., X.H., M.R.B. and J.A.R. wrote the manuscript.
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Integrated supplementary information
Supplementary Figure 1 Machining of the cannula holder adapter.
This adapter is specifically designed for use with the KOPF Model 1966 Cannula Holder. The adapter is fashioned from aluminum with an 8 mm stalk (3 mm in diameter) that can be held by the Model 1966. The main body of the adapter is 14 mm in length with a 7 mm diameter. There are two orthogonal bore holes through the body. The first is a 5 mm hole from which the center slit is created through to the tip of the adapter. The second is a 2 mm screw-hole so that a screw can be tightened to reduce the size of the center slit to hold the μ-needle. It is important that the center point of the adapter be in-line with the center point of the cannula holder itself to ensure accurate device injection. Note that this adapter is merely a suggestion, but we acknowledge there can be many other solutions to the problem of accurate injection of the devices. Most stereotaxic instrument manufacturers offer custom-built holders and it is likely that many standard electrode holders can be modified to suit the needs of the individual laboratory (e.g. KOPF Model 1768).
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McCall, J., Kim, Ti., Shin, G. et al. Fabrication and application of flexible, multimodal light-emitting devices for wireless optogenetics. Nat Protoc 8, 2413–2428 (2013). https://doi.org/10.1038/nprot.2013.158
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DOI: https://doi.org/10.1038/nprot.2013.158
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